The scientific theme for this competitive renewal continues the theme from the grant submission: effects of exposures to environmentally hazardous substances on reproduction and development in humans and wildlife. Special emphasis is placed on substances commonly encountered as a result of improperly managed waste disposal. The chemicals under study are organics, both halogenated and nonhalogenated compounds. The program will focus on the underlying mechanics of xenobiotics/ endocrine interactions and their effects to allow a better understanding of the implications of perturbations of reproductive and developmental processes by hazardous substances in the environment. Nine projects (5 biomedical and 4 nonbiomedical) will study: 1) Epidemiologic studies of neurodevelopment of a population exposed to perchlorethylene (PCE, a peroxisome proliferators) in drinking water, and epidemiologic techniques to study similar environmental problems (two biomedical projects);2) receptor based mechanistic studies of the role of intracellular receptors and signaling pathways in the development of organisms and tissues (receptors/pathway: Ah receptor, AhR;peroxisome proliferator activated receptor, PPAR;estrogen receptor, ER;androgen receptor, AR;MAP kinase pathway) for important xenobiotics (planar halogenated aromatic hydrocarbons, PHAHs;polycyclic aromatic hydrocarbons, PAHs;and peroxisome proliferators, especially phthalates), and three biomedical projects;3) Mechanisms of toxicity and resistance of fish populations to PHAHs and xenoestrogens involving receptors (AhRs, PPARs, and ERs) and cytochrome P450s (1 non-biomedical project and 2 biomedical);4) studies of the mechanistic basis for reproductive and developmental effects on observed wildlife (including those mediated by AhR and ER) exposed to a complex mixture in surface water from a Superfund Site via groundwater and sediment (1 non-biomedical);5) Mechanisms of oxidative dechlorination by an abiotic non-heme iron catalyst for remediation of a wide variety of xenobiotics, including all those under study in other projects.